Specific fluorescence release based on synergistic activation of enzymes and position-dependent of electrophilic groups to diagnose intrahepatic cholestasis of pregnancy

Wen, Ying; Long, Zhiqing; Bai, Xuefeng; Huo, Fangjun; Yin, Caixia

doi:10.1016/j.cej.2022.135978

Cited by 11 publications

(3 citation statements)

References 32 publications

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“…Molecular fluorescent probes have attracted much attention due to their high sensitivity and high selectivity, enabling accurate identification of target analytes and noninvasive real-time observation in vivo . − Reactive oxygen species (ROS) and reactive nitrogen species (RNS) levels increase during the progression of RA disease. − Several fluorescent probes for the detection of reactive oxygen and nitrogen species have been reported for the diagnosis and monitoring of arthritis. ,− In physiological disorders, activated macrophages produce high levels of nitric oxide (NO), which can upregulate osteoclasts, destroy cartilage, and recruit other immune cells to cause inflammation, and thus NO is often thought to be involved in joint damage. − Therefore, the detection of NO is of great significance for the early diagnosis of RA. , The reported NO probes are mainly composed of o -phenylenediamine and aromatic secondary amines, which specifically react with NO to produce fluorescent signals. − Among them, probes with o -phenylenediamine structure are typically based on photoinduced electron transfer (PET) that undergo enhanced fluorescence in the presence of NO. − Compared with to the single-channel imaging mode of the “turn-on” type probes, the ratio-metric fluorescent probes based on the intramolecular charge transfer (ICT) effect are preferred for NO imaging with high-resolution and self-calibration, which can be quantitatively detected by the ratio and effectively reduce the background signal interference to realize accurate spatial-temporal detection of NO. − However, ICT-based small molecule NIR fluorescent probes with o -phenylenediamine have not been reported.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial-Targeted Ratiometric Near-Infrared Fluorescence Probe for Monitoring Nitric Oxide in Rheumatoid Arthritis

Han,

Sun,

Zhao

et al. 2024

J. Med. Chem.

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Rheumatoid arthritis (RA) is a destructive autoimmune disease, where nitric oxide (NO) is closely implicated in the inflammatory processes of RA. Therefore, direct visualization of NO is essential to assess the pathological changes in RA. Herein, a mitochondrial-targeted near-infrared ratiometric fluorescent probe (NFL-NH 2 ), based on the intramolecular charge transfer effect, was synthesized and applied to monitor the changes of NO content in early RA. Specially, probe NFL-NH 2 showed a 44-fold fluorescent intensity ratio (I 705 /I 780 ) response toward NO with a detection limit of 0.536 nM, enabling qualitative and quantitative analysis of NO. Additionally, NFL-NH 2 can accurately target mitochondria and sensitively detect exogenous and endogenous NO in RAW 264.7 cells. Notably, in vivo RA monitoring assays demonstrated that NFL-NH 2 can rapidly detect NO levels associated with the inflammatory damage degree in RA mice models by ratiometric fluorescence imaging. These results validate that NFL-NH 2 holds significant potential for diagnosing NO-mediated RA diseases.

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Section: Introductionmentioning

confidence: 99%

Mitochondrial-Targeted Ratiometric Near-Infrared Fluorescence Probe for Monitoring Nitric Oxide in Rheumatoid Arthritis

Han,

Sun,

Zhao

et al. 2024

J. Med. Chem.

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“…We selected basic blue 3 (BB3) as fluorophores based on their excellent fluorescence properties known from our previous live-cell/tissue imaging and clinical blood analysis. [40] And, a series of off-on probes having different R substituents in the amide group (Figure 1C) were designed and synthesized to screen the probe with superior analytical performance and provide a systematic and comprehensive view on whether and how different components (R group, Figure 1B) design might affect the probe's response to CE. The probe J Fast (Figure 1C) exhibited the optimal property combination of selectivity and response rate toward CE.…”

Section: Introductionmentioning

confidence: 99%

A Space‐Dependent ‘Enzyme‐Substrate’ Type Probe based on ‘Carboxylesterase‐Amide Group’ for Ultrafast Fluorescent Imaging Orthotopic Hepatocellular Carcinoma

et al. 2023

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Fast and selective fluorescence imaging for a biomarker to related-disease diagnosis remains a significant challenge due to complex physical environment. Human carboxylesterase (CE) is expected to be a potential biomarker of hepatocellular carcinoma (HCC) to improve the accuracy of diagnosis. However, existing probes for CE has slow response rate and low selectivity. Herein, the amide group is selected as CE-responsive sites based on the "substrate-hydrolysis enzymatic reaction" approach. From a series of off-on probes with leave groups in the amide unit, probe J Fast is screened with the optimal combination of rapid response rate and high selectivity toward CE. J Fast requires only 150 s to reach the maximum fluorescence at 676 nm in the presence of CE and free from the interference of other esterase. Computational docking simulations indicate the shortest distance between the CE and active site of J Fast . Cell and in vivo imaging present that the probe can turn on the liver cancer cells and tumor region precisely. Importantly, J Fast is allowed to specifically image orthotopic liver tumor rather than metastatic tumor and distinguish human primary liver cancer tissue from adjacent ones. This study provides a new tool for CE detection and promotes advancements in accurate HCC diagnosis.

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“…Chemical labeling is generally achieved via a reaction between the fluorophore and an active group (e.g., amino and thiol) in the protein structure. [15] Although this method affords a smaller label and a more efficient binding mode, the fluorescence interferes with other small molecules, including GSH [16] and cysteine, owing to their greater reactivity compared with enzymes. In addition, the non-specific response between the chemosensor and enzymes also leads to the generation of false positive signals and reduce the SBR.…”

Section: Introductionmentioning

confidence: 99%

A Fluorescent Chemosensor for Long‐Term Tracking of Cancer Cell Metastasis and Invasion via Enzyme‐Activated Anchoring

Liu

Xia

Wang

et al. 2023

Adv Funct Materials

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Evidence shows that the enzyme human cytochrome P450 1A1 (CYP1A1) is associated with cancer; indeed, it is shown to play a key role in the occurrence of many cancers. Therefore, the molecular imaging of CYP1A1 in cells is of great significance for revealing the process of cancer development. Herein, a chemosensor, DCBEM, is reported that is able to selectively recognize CYP1A1 and achieve long‐term labeling of the enzyme through an enzymolysis cascade reaction. The design of DCBEM relies on the reaction between the highly electrophilic intermediate (quinone methide) and the enzyme, which forms a fluorescent label with CYP1A1 via covalent bonding. The chemosensor reveals excellent specificity toward CYP1A1 and achieves high‐resolution monitoring of cell migration with a strong retention capacity in vivo (up to 4 days). Further, using DCBEM, the pathways of invasion of colon cancer and breast cancer cells are successfully visualized in living mice. This method of labeling enzymes provides a simple and efficient way to render ordinary fluorescent chemosensors suitable for the long‐term tracking of cancer cells, for which such molecular tools are currently lacking.

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Specific fluorescence release based on synergistic activation of enzymes and position-dependent of electrophilic groups to diagnose intrahepatic cholestasis of pregnancy

Cited by 11 publications

References 32 publications

Mitochondrial-Targeted Ratiometric Near-Infrared Fluorescence Probe for Monitoring Nitric Oxide in Rheumatoid Arthritis

Mitochondrial-Targeted Ratiometric Near-Infrared Fluorescence Probe for Monitoring Nitric Oxide in Rheumatoid Arthritis

A Space‐Dependent ‘Enzyme‐Substrate’ Type Probe based on ‘Carboxylesterase‐Amide Group’ for Ultrafast Fluorescent Imaging Orthotopic Hepatocellular Carcinoma

A Fluorescent Chemosensor for Long‐Term Tracking of Cancer Cell Metastasis and Invasion via Enzyme‐Activated Anchoring

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